CN102939044B

CN102939044B - For characterizing cornea and manufacturing the system of eye-use lens

Info

Publication number: CN102939044B
Application number: CN201080018948.XA
Authority: CN
Inventors: J·F·比勒
Original assignee: Perfect Ip Co Ltd
Current assignee: Perfect Lance Ltd.; Perfect IP LLC
Priority date: 2009-03-04
Filing date: 2010-03-04
Publication date: 2016-01-20
Anticipated expiration: 2030-03-04
Also published as: US20150112203A1; CN102438549B; US9192292B2; CA2754774C; CA2754774A1; KR101624091B1; CN105105869A; US20110130677A1; KR20150036802A; EP2405798A1; KR20150038595A; HK1215527A1; JP5778797B2; JP5462288B2; US20110130654A1; CN105147239A; HK1180927A1; BRPI1006732B1; EP2421472B1; CN102438549A

Abstract

The invention discloses a kind of system for measuring cornea eye shape, with having at least one that irradiated corneal moieties can be made to produce in the front surface of Infrared irradiation eyes of the wavelength of fluorescence, rear surface and interior zone.Detect the fluorescence of generation subsequently.Its irradiating step is included in focused IR light in the multiple different planes substantially vertical from eye optical axis.Front surface at least partially, at least partially rear surface of cornea and/or the topography of a part of interior zone can be made according to the light detected.The definition that autofluorescence can determine vision is produced by making the albumen in amphiblestroid pigment epithelium cell.

Description

For characterizing cornea and manufacturing the system of eye-use lens

intersect and apply for

The application requests the rights and interests of following U.S. Provisional Application: submit on March 4th, 2009 61/209,362, submit on March 4th, 2009 61/209,363, submit on May 27th, 2009 61/181,420, submit on May 27th, 2009 61/181, submit on May 27th, 519 and 2009 61/181,525.These U.S. Provisional Applications all form a part herein by reference at this.But, description below and the disclosure of these provisional application inconsistent time, be as the criterion with description below.

Background technology

The known multiple system for characterizing cornea, and utilize the information characterized to make eye-use lens.See, such as U.S. Patent number 6413276,6511180,6626535 and 7241311.

The impact of the moisture that the difficult point of system becoming known for characterizing cornea exists when being that the characteristic of people's cornea can be subject to measuring.Thus, such as, be patient when making eye-use lens, if what characterize is the cornea of patient under the dry ocular environment of patient, so when patient's eye contains large quantity of moisture, these lens will be not suitable for patient.

Another problem of conventional system does not usually consider the internal structure of cornea.We think that the focusing effect of cornea is jointly realized by the internal structure of the front surface of cornea, the rear surface of cornea and cornea, have played about 80%, 10% respectively, and the effect of 10%.Do not consider the way of the internal structure of cornea, and do not consider the way of shape of posterior surface of cornea in some cases, will the lens that gratifying vision cannot be provided be obtained.

Therefore, need the system for characterizing cornea providing a kind of improvement, object is the obtained eye-use lens can inserting human eye.More preferably, this system can analyze the effectiveness of the lens that place focused light on the retina.

The present invention also comprises a kind of system for measuring patient's vision definition, revises the effectiveness of thing with the eye determining to implant lens or other supply patients.According to this method, irradiate patient's eye with the scanning ray that can produce the wavelength of fluorescence on the retina, detect the definition of the image that fluorescence produces with such as photodetector.Fluorescence is produced by the protein in amphiblestroid pigment epithelium cell and amphiblestroid photoreceptor.

Subsequently, the path of adjustment scanning ray, to increase the definition of the image that fluorescence produces.The common wavelength of scanning ray is 750 to about 800nm, is preferably about 780nm.

Summary of the invention

The invention provides a kind of system meeting described demand.This system comprises a kind of method and apparatus for measuring cornea eye shape, and wherein, cornea has a front surface, a rear surface and an interior zone between front and rear surface.This method depends on the fluorescence that cornea produces, and determines that the prior art of cornea shape is different from adopting the reflection coefficient of incident illumination.According to the method, with having at least one that irradiated corneal moieties can be made to produce in the front surface of the Infrared irradiation cornea of the wavelength of fluorescence, rear surface and interior zone.Detect the fluorescence produced.The shape figure of the front surface of cornea, rear surface and/or interior zone is made of the fluorescence detecting." front surface " refers to eyes surface outwardly." rear surface " is backward towards retina.

Such as, in the example of the front area of cornea, measure the optical path length of multiple position in interior zone.The existence of the blue light that interior zone produces indicates the existence of collagen protein thin layer in cornea.

Preferably, the step of irradiation is included in focused IR light in the multiple different planes substantially vertical from the optical axis of eyes.These planes can be staggered with the interior zone of the rear surface of the front surface of cornea, cornea and/or cornea.

The present invention also comprises the equipment implementing the method.Preferred equipment comprises laser instrument, focusing arrangement and detector, and laser instrument will have the selected part that irradiated corneal moieties can be made to produce the Infrared irradiation cornea of the wavelength of fluorescence; Focusing arrangement as condenser lens, focused ray in the selected part of cornea; And detector is as photodiode detector, detect the fluorescence produced.

The present invention also comprises a kind of system for measuring patient's vision definition, revises the effectiveness of thing with the eye determining to implant lens or other supply patients.According to the method, irradiate patient's eye with having the scanning ray that can make wavelength retina producing fluorescence, and detect the definition of the image that fluorescence produces with such as photodetector.Fluorescence is produced by the albumen in amphiblestroid pigment epithelium cell and amphiblestroid photoreceptor.Subsequently, the path of adjustment scanning ray, to increase the definition of the image that fluorescence produces.The common wavelength of incident illumination is 750 to about 800nm, is preferably about 780nm.Word " vision definition " refers to the ability that experimenter distinguishes two images (white is 100% brightness, and black is 0% brightness) that brightness is different.The contrast difference (relative brightness) that experimenter can discover two different images is less, and the vision definition of experimenter is higher.

Accompanying drawing explanation

These and other features of the present invention, various aspects and advantage better can be understood in conjunction with the claim of description below, annex and accompanying drawing, wherein:

Fig. 1 is the schematic diagram of the method for the present invention for pseudophakic eye;

Fig. 2 is the graphic representation of the spherical aberration that the crystalline lens of the postoperative eyes of human eye and laser vision correction exists;

Fig. 3 is the schematic diagram of a kind of account form determining retinal images definition;

Fig. 4 is the audio-visual picture of the mathematical routine that can be used for the convolution determined in the computational methods of vision definition;

Fig. 5 illustrates the side cross-sectional view as the Stress distribution in the load cornea of finite element modeling (FEM) result;

Fig. 6 is the schematic diagram of the physical process of display Second Harmonic Imaging (SHGi) and Two-photon excitation fluorescence imaging (TPEFi);

Fig. 7 show schematically show Two Photon Fluorescence used in the present invention/Oph critical piece;

Fig. 8 is the synoptic chart of the SHGi of collagen tissue structure;

Fig. 9 shows the micromorphometry feature of cornea;

The visual field that Figure 10 shows the size of the intraocular lens (C-IPSM) in similar customization makes the schematic diagram of synthesis cornea shape figure; And

Figure 11 is the schematic diagram of the system for detecting the image definition obtained by the lens implanting ophthalmic.

Detailed description of the invention

general introduction

One is used for the system determining corneal topography (comprising the front and rear surface of cornea and the topography of interior zone), comprises mensuration and simulation steps, provides the value that intracorneal refractive rate distributes.Statistical distribution and the result of the finite element modeling of cornea internal stress/strain stress relation can be adopted.

The equipment that the present invention uses can be Two Photon Fluorescence, to obtain the measurement result of multiple high spatial resolution.The each independent light beam that equipment adopts has unique optical path length.The method of Second Harmonic Imaging (SHGi) and Two-photon excitation fluorescence imaging (TPEFi) can be adopted.Utilize these to measure the multiple pixel datas produced, the detailed spatial distribution of the refracting characteristic of cornea can be assessed, therefore can make the intraocular lens of the aberration that energy fine compensation detects.

This system also comprises the method for measuring intraocular lens effectiveness, such as, and method of quality control.

characterize cornea

First referring to Fig. 1, that schematically shows lens for the measuring implantation system as the refracting characteristic of the intraocular lens of customization, and be labeled as 10.Multiple light beam 40 propagates across the pseudophakic eye in the intraocular lens 20 implanting customization, and these lens can high spatial resolution the optical path length of each light beam of partial correction.These light are conducted through described pseudophakic eye, and retina 30 forms image.The feature of multiple independent light beam 40 is that each light beam has unique optical path length.More specifically, each optical path length represents the refraction that it experiences during propagating through eyes of each light beam.Next, collect whole optical path length with computer, create the digitized image on the retina of eyes.Multiple light beam 40 propagates through the front surface 12 of cornea 14, the interior zone 13 of cornea 14, the rear surface 16 of cornea 14 in order and has the intraocular lens of customization of front surface layer 22, and forms focusedimage on retina 30.Be 12/717 at the application number submitted on the same day, 886, be entitled as in the co-applications of the applicant of " making and regulate the system of lens and lens obtained thus " (files 19780-1) and describe the method making lens 20, the document forms a part herein at this by introducing.

On the top of multiple light beam 40, show three adjacent beams 42,44, and 46, represent a regional area in partition method.As a rule, in the ray tracing of high spatial resolution calculates, number to be assessed with light necessarily according to their optical path length in human eye.For the object calculated, selected a datum level 18 close to the natural pupil of pseudophakic eye, the thus optical path length of the single light beam of standardization.More specifically, single light can be expressed as exp (ix (2 π/λ) xn (x from pupil plane 18 to the propagation of table 22 before the intraocular lens 20 of customization, y) xz (x, y)), wherein exp is similar to exponential function, i represents imaginary number number of unit, π equals about 3.14, λ represents the wavelength of light, n (x, y) represent local indexes of refraction, z (x, y) denotation coordination is the actual range of the lateral attitude distance pupil plane 18 of x and y.Physical length z (x can be used, y) intraocular lens (C-IPSM) 20 that value expresses customization occur during lens are implanted to any mistake of axis or lateral attitude or the relevant location that tilts, also available optical technology compensates this type of mistake by finely tuning top layer 22 in body, this kind of optical technology is such as be 12/717 at the above-mentioned application number submitted on the same day, 886, be entitled as " make and regulate lens system and thus obtain lens " (files 19780-1) applicant co-applications described in, the document at this by being introduced as a part herein.

Fig. 2 shows a kind of special optical aberration of the human eye existed in the eyes (cornea as through shaping) after normal eye (as crystalline lens) and laser in situ keratomileusis, as spherical aberration, show the induction of the spherical aberration in the eyes after laser in situ keratomileusis 60.In the upper part of Fig. 2, citing shows the situation of normal eye 50.Eyeball 52 comprises cornea 56, lens 54 and retina 58.Usually, for the pupil diameter of 6mm, introduce the spherical aberration 59 of about wavelength X of corresponding 0.5 μm, it is main relevant to lenticular spherical shape.In the lower part of Fig. 2, when experienced by myoporthosis postoperative eyes 60, illustrate the introducing of a large amount of spherical aberrations.Eyeball 62 has cornea 66, lens 64 and retina 68.Usually can run into the spherical aberration of about 10 wavelength X (10 λ) of corresponding 5 μm, it is main relevant to the edge of the cornea of central flat.

Fig. 3 is the schematic diagram of the computed path 70 of the required refraction effect determining the lens implanted.Multiple light beam 72 converts a pupil function 74 to, the spatial distribution of path 76 can be envisioned as, and can express by mathematical expression 78: P (x, y)=P (x, y) exp (ikW (x, y)), wherein P (x, y) be amplitude, exp (ikW (x, y)) is the phase place of synthesis pupil function.Phase place depends on wave vector k=2 π r/ λ, and λ is the wavelength of single light beam, and W (x, y) is its path, and i represents imaginary number number of unit.Point spread function (PSF) 80 can be derived from pupil function 74, mathematically can be expressed as Fourier transformation 82:PSF (x, y)=| FT (P (x, y)) | ², also diagrammatically can be expressed as pseudo-three-dimensional function 84, show the situation close to diffraction limited, illustrate that pseudophakic eye only has less optical aberration.Si Telieer can according to 88:i=(max (PSF (x from calculating formula 70 than i86, y))/max (PSFdiff (x, y)) derive, wherein PSF (x, y) point spread function of the optical system of aberration is indicated, PSFdiff (x, y) is similar to the optical system of Utopian diffraction limited.Point spread function (PSF) 80 and Si Telieer can be used for the optical property of visualize eyes and the definition of retinal images than i86.

Fig. 4 is the audio-visual picture of the mathematical procedure that can be used for the convolutional calculation evaluating and testing retinal images definition.Imaging process 90 can intuitively turn to the Mathematical Calculations being called convolution 94, wherein by each picture point of winding and the point spread function PSF96 of optical system, can the idealized image of obfuscation object 92, and obtain image 100.When having the human eye of 6mm pupil diameter, PSF96 is shown as pseudo-three-dimensional Figure 98.Thus, the definition of retinal images 100 can be confirmed by point spread function PSF96.

Fig. 5 illustrates the side cross-sectional view as the stress and strain distribution in the load cornea of finite element modeling (FEM) result.With the distribution of the stress 104 on finite element modeling (FEM) algorithm 102 fictitious load cornea with strain 106, the local density of cornea internal matrix tissue can be measured, spatial distribution n (the x of refractive index can be derived from this density, y), the variable measurement result of the optical path length of multiple light beam in cornea is obtained.First, finite element modeling (FEM) provides the distribution of the stiffness parameters in the elementary volume, volume element proportional with local organization density.Such as at the Biomechan.ModelMechanobiology5237-246 of the people such as A.Pandolf, describe FEM in 2006 and be modeled in application in its biological mechanics.The same intraocular pressure applying 2 kPas of (kPA) (15mmHg) on rear surface.Only Bowman's layer 108 is complete is fixed on edge.In the left-hand component of Fig. 5, show the cauchy stress distribution in radially direction; The scope of absolute value is-2.5kPa to+2.5kPa.On the right-hand component of Fig. 5, show maximum principal strain distribution; The relative compression of matrix organization or expansion are between-0.07 to+0.07.

cornea is characterized by fluorescent emission method

Fig. 6 is the schematic diagram of the physical process of display Second Harmonic Imaging (SHGi) and Two-photon excitation fluorescence imaging (TPEFi).In the upper left-hand of Fig. 6, show the principle of Second Harmonic Imaging (SHGi) 140.Adding frequency is consistently ω _ptwo-photon 146 and 148, produce instantaneous from energy level 144 be radiated to again 142 there is frequency 2 ω _pphoton 150.In the upper right of Fig. 6, visualize Two-photon excitation fluorescence imaging (TPEFi) process.I starves ω frequency _ptwo-photon 156 and 158 molecule is excited to excitation level 154 from ground state level 152.Because molecule is de-energized to energy level 162 in about 1 nanosecond, therefore in about 1 picosecond after heat radiation to energy level 160, fluorescent photon ω _fradiation again.In the lower part of Fig. 6, be illustrated the wavelength dependency of the imaging process of SHGi (second harmonic generation) and TPEFi (two-photon fluorescence excitation).Usually, because frequency is ω _pthe wavelength of irradiation femtosecond laser beam be down to 170 from 166 through 168, frequency is 2 ω _pthe intensity of SHGi signal 174,176 and 178 and frequency be ω _ftPEFi signal 182,184 and 186 intensity increase.In two-photon corneal microscope/ophthalmoscope, as described in Figure 7, the irradiation femtosecond laser that uses wavelength to be 780nm, to optimize the contrast of the imaging that cornea internal sizes fibril and cell are dashed forward.

Fig. 7 schematically shows the preferred equipment 702 of the intraocular lens customized for characterizing cornea design.Equipment 702 comprises laser instrument 704, preferred two-photon laser; Control unit 706 and scanning element 708.Two-photon excitation microscope is a kind of Imaging-PAM, can the degree of depth of imaging viability tissue to 1 millimeter.Two-photon excitation microscope is the microscopical a kind of special model of multiphoton fluorescence.Two-photon excitation organizes deep-going because it is darker, effective light detects and less phototoxis and be better than confocal microscopy method.The conceptual foundation of two-photon excitation is the fluorogen that the two-photon of mental retardation can excite in a quantum rank, causes fluorescent photon usually to launch than any one the higher energy in two excitation photon.The probability of the nearly simultaneously stability of two-photon is very low.Therefore, usually needing high-throughout excitation photon, is usually femtosecond laser.

Suitable laser instrument can from California, USA Sani Wei Er CalmarLaser company.Persistent period of each pulse that this laser instrument sends is about 50 to about 100 femtoseconds, and energy level is at least about 0.2nJ.Preferably, laser instrument 704 is the pulse of 780nm at about 5,000 ten thousand wavelength of interior generation per second, and pulse length is about 50fs, and the pulse energy of each pulse is about 10nJ, and laser instrument is 500mW laser instrument.The laser beam 720 sent is directed across neutral colour filter 724 with strobe pulse energy by deviation mirror 722.The normally about 2mm of diameter of the laser beam 720 that laser instrument sends.Subsequently, laser beam 720 is through dichroic mirror 728, and then arrive scanning element 708, pulse is spatially scattered in the light beam of various ways by scanning element 708.Computer control system 730 gated sweep unit 708, the cornea 732 in scanning eye.

The diameter of the light beam 720 that laser instrument sends is approximately 2 to 2.5mm.The light beam 720 leaving scanner 708 is focused into the size being applicable to scanning cornea 732 subsequently by focusing arrangement, normally diameter is the light beam of about 1 to 2 μm.Focusing arrangement can be arbitrarily series can be used to reduce laser beam to the lens of ideal dimensions and optical device, as prism.Focusing arrangement can be flexible lens to 742 and 744 and microscope objective 746, wherein the second deviation mirror 748 guide light beam from lens to arrival microscope objective.Focusing microscope object lens can be the operating distances of 40x/0.8 is the object lens of 3.3mm.Scanning and control unit are preferably positioned at the HeidelbergSpectralisHRA scanning element of the HeidelbergEngineering company of Heidelberg, Germany.

There is in optics in scanning element the region that can scan without the need to mobile cornea 732 or Optical devices that one piece of diameter is about 150 to 450 μm.In order to scan other regions of cornea, must in x, y plane mobile cornea.Meanwhile, in order to scan the different depth of cornea, the focal plane of laser scanner must be moved in a z-direction.

Control unit 706 can be any computer, comprises memorizer, processor, display and input equipment, as mouse and/or keyboard.Control unit is programmed, makes the laser beam tool pattern in need from scanning element 708.

Cell on cornea 732 front surface will send fluorescence under the exciting of the laser beam of 780nm, produce the green glow of about 530nm wavelength.The light sent advances along the path of incident laser, namely, incident illumination is through microscope objective 746, be diverted mirror 748 and be reflected through lens 744 and 742, dichroic mirror 728 is entered through scanning element 708, dichroic mirror is by fluorescent reflection to path 780, and the path usually and through the incident illumination of dichroic mirror 728 is at a right angle.In path 780, the light sent is through light filter 782, and filtering has the light of unwanted frequency, arrives photodetector 786 subsequently by condenser lens 784.Photodetector can be avalanche photodide.In the memorizer that the data that photodetector obtains can be stored in computer control unit 730 or other memorizeies.

Thus, with the front surface of Infrared irradiation cornea with the wavelength that can produce fluorescence, the fluorescence produced is detected.Concerning front surface, incident infrared light focuses in basic perpendicular from eye optical axis multiple different plane, and wherein the front surface of these planes and cornea is staggered.

Can characterize rear surface by identical step, focused IR light in basic perpendicular from eye optical axis multiple different plane, wherein the front surface of these planes and cornea is staggered.In the enterprising line scanning of plane that 64 are separated, wherein scan with the light beam that interval is approximately 3 microns.

What the difference of scanning cornea inside was that collagen protein thin layer in interior zone produces is blue light but not green glow.The wavelength of blue light is approximately 390nm.When scanning cornea and being inner, another light filter 732 must be used to confirm that blue light all arrives photodetector 786 through light filter.

Fig. 8 is the synoptic chart of the SHG imaging of collagen tissue structure.At upper left-hand visualize collagen three spiral 188 of Fig. 8, show the typical structure of collagen fiber.Collagen fiber are organisms of the three-layer laminated structure of the synthesis being positioned at corneal stroma inside.In the lower left side of Fig. 8, show second harmonic and the interactional process of (SHG) laser/collagen fiber occurs.Frequency is that the photon 194 of ω makes fiber polarization far away to intermediate level 196, but second photon 198 of same frequency ω also creates the electron energy level 192 of moment.Electron excitation is become the photon 200 of double energy by radiation more immediately, and frequency is 2 ω.Due to the unidirectional shape of collagen fiber, this process is made to obtain higher productive rate.Recently Second Harmonic Imaging (the SHGi) (M.Han of cornea tissue has been reported, G.Giese, and J.F.Bille, " Second Harmonic Imaging of the collagen fiber in cornea and sclera ", Opt.Express13,5791-5795 (2005)).Measure with the equipment of Fig. 7.Equation 224 according to opening from the nonlinear optics polarization 226 of collagen fiber measures SHGi signal.Signal intensity 228 and second order polarization item [χ ⁽²⁾⁾] ²direct one-tenth positive example, is inversely proportional to the pulse length π of femto-second laser pulse.Like this, as described in Figure 7, due to the ultrashort pulse length of femtosecond laser used in the strong unipolarity of collagen fiber and two-photon corneal microscope/ophthalmoscope, the SHGi image of high-contrast shows the three-layer laminated structure of corneal stroma intuitively.

Anatomically, Fig. 9 shows the cornea 14 of eyes, comprises epithelium 230 from its front surface 12 to its rear surface 16, Bowman's layer 244, substrate 246, Descemet's membrane 248, and endothelium 250.Epithelium 230 is made up of multiple cellular layer, as being incorporated to the cellular layer 232,234,236,238 and 240 in basal-cell layer 242.The two-photon excitation autofluorescence pattern (TPEF) of two-photon corneal microscope can blur-free imaging basal-cell layer 242 and front surface 12, can obtain the measurement result of the spatial discrimination of the thickness of epithelium 230.Also the two-photon excitation autofluorescence mode imaging endothelium of available two-photon corneal microscope, obtains the measurement result of the spatial discrimination of the thickness of cornea 14.Substrate 246 forms by close to 200 collagen protein thin layers, as 252,254,256,258,260,262 and 264, has the three dimensional structure of synthesis, can utilize Second Harmonic Imaging (SHGi) mode evaluation of two-photon corneal microscope.Based on these measurement results, as Fig. 5 exemplify, under the support of the finite element modeling (FEM) of collagen structure rigidity, the distributed in three dimensions of the refractive index of cornea inside can be reconstructed.Thus, the optical path length of multiple light beam in cornea inside in ray tracing calculating can be measured by high spatial resolution.Thus, the topography of the front surface of cornea, rear surface and/or internal structure can be drawn.

In Fig. 10, the synthesis cornea shape Figure 27 0 formed by multiple monomer imaging region is shown.Usually, central imaging area 280 extends beyond the diameter of about 2mm, comprises close to 2000x2000 imaging pixel, amounts to 400 ten thousand imaging points or pixel, obtains the resolution (as used Nikon 50x/0.45 microscope objective) close to 1 μm.Cornea shape Figure 27 0 of synthesis comprises the three-dimensional stacked of Two Photon Fluorescence image, is made up of Two-photon excitation fluorescence imaging (TPEFi) or Second Harmonic Imaging (SHGi)-imaging model.In order to mate the size of diameter close to the intraocular lens of the customization of 6mm, have employed 6 peripheral imaging regions 290,292,294,296,298 and 300.The cross correlation algorithm of the gray value pixel of the running time in crossover region 310,312,314,316,318 and 320 is utilized to realize the location of monomer region.Thus, synthesis corneal topography has close to 2,000 8 hundred ten thousand data, provides the composograph of the spatial discrimination of a transverse slice through cornea.Usually, the optical path length of the described light beam when the cornea of multiple light beam by pseudophakic eye is reconstructed by 100 transverse slice through cornea.

designing and making lens

The method of the design data lens obtained according to the equipment of Fig. 7 is known in the art, and includes the United States Patent (USP) 5,050 that Roffman proposes, method described in 981, for these method document at this by being introduced as a part of the present invention.United States Patent (USP) 12/717,886(files 19780-1 in the aforesaid co-applications of applicant) in also illustrate make or adjustment lens method.

the mensuration of vision definition

Referring to Figure 11, which schematically illustrates a kind of system of the vision definition for measuring patient, in the example of Figure 11, also there is the intraocular lens 1102 of implantation.System for this is basic identical with the equipment shown in Fig. 7, employs identical laser instrument 704 and scanner 708.Optionally, adaptive optics module (AO module) 1104 can also be used for the object simulating the refraction correction effect relevant to image definition and depth of focus.For the object of the single light beam that precompensation laser instrument 704 produces, AO module 708 is made up of phase-plate compensator and flexible mirror.At the United States Patent (USP) 7,611 of applicant, in 244, describe the self-reacting device being used for the intrafascicular asymmetric aberration of compensating light used in the present invention.At the United States Patent (USP) 6,155 of applicant, in 684, describe the method and apparatus of the refracting characteristic with adaptive optics feedback control precompensation people.At the U.S. Patent number 6,220 of applicant, in 707, describe the use of flexible mirror.Single light beam 1112, through cornea 1114, is followed by intraocular lens 1102, focuses on the retina, forms retinal images 1120.Wavelength due to the light entered is about 750 to about 800nm, is preferably about 780nm, and the fluorescin in pigment epithelium cell and photoreceptor will send the fluorescence that frequency is about 530nm to about 550nm.Figure 11 line 1122 shows the light sent.The intensity of the fluorescence sent indicates the situation that cornea 1114 and intraocular lens 1102 focus on the light beam entered, and finds out corresponding relation wherein, and wherein higher intensity illustrates better focusing.In order to measure the focusing whether be improved, in order to increase the definition of the image that fluorescence produces, the path of the scan light entered such as can be changed by the phase-plate in adjustment adaptive optics module 1104 or flexible mirror.

Optionally, vision can be provided to stimulate 1124, as Snellen chart, obtain the objective feedback of patient in vision definition.

Utilize the method, implantation lens can be measured, as artificial intraocular lenses (IOL), corneal lens or contact lens, and the effect of the modification of original position lens (cornea, IOL and natural lens lens).

Although preferred embodiment describe the present invention in detail, other embodiment also may be there is.Such as, although be the purposes of corresponding intraocular lens to describe the present invention, be appreciated that acquisition also can be used for making contact lens for the data characterizing cornea and other implants the lens of eyes.Therefore, the scope that claim of the present invention is protected should not be subject to the restriction of comprised description related to the preferred embodiment here.

Claims

1. one kind makes cornea eye (14,56,732) method of topography, described cornea (14,56,732) interior zone (13) that there are front surface (12), rear surface (16) and be positioned between described front surface (12) and rear surface (16), this method comprises the following steps:

A) cornea (14 is irradiated, 56,732) a part, this is by using the infrared ray (40 focused on, 720) cornea (14 is scanned, 56,732) the multiple Different Plane perpendicular to eye optical axis in described part realize, described multiple plane and following partial intersection:

I) Part I of described front surface (12) and the Part I of described interior zone (13),

Ii) Part II of described front surface (12), the Part II of described interior zone (13) and the Part I of described rear surface (16), and

Iii) Part II of described rear surface (16) and the Part III of described interior zone (13),

Wherein said infrared ray (40,720) has the wavelength producing fluorescence and second_harmonic generation imaging signal from irradiated cornea (14,56,732) part via nonlinear optics process;

B) detect fluorescence and detect and assess the second_harmonic generation imaging signal produced from irradiated cornea (14,56,732) part;

C) from the fluorescence detected, determine the measured value of the shape of front surface (12) and rear surface (16) and the spatial discrimination thickness of irradiated cornea (14,56,732) part;

D) from second_harmonic generation imaging signal, determine the three-layer laminated structure of the corneal stromal tissue in irradiated cornea (14,56,732) part;

E) by using finite element modeling to draw reflectance n (x, y) spatial distribution, the optical path length (76) of irradiated cornea (14,56,732) part is determined from the fluorescence detected and second_harmonic generation imaging signal;

F) from the irradiated cornea (14 generated, 56,732) topography of front surface (12), rear surface (16) and interior zone (13) is generated in the spatial distribution of the optical path length (76) of part.

2. method according to claim 1, wherein said nonlinear optics process comprises two-photon excited fluorescence imaging processing and detecting step, described detection and appraisal procedure comprise the green glow detecting and produce arbitrarily, the appearance of wherein said green glow indicates described cornea (14,56,732) front surface (12) or rear surface (16).

3. method according to claim 1, wherein said nonlinear optics process comprises two-photon excited fluorescence imaging processing and detecting step, described detection and appraisal procedure comprise the blue light detecting and produce arbitrarily, wherein the existence of blue light indicates cornea (14,56,732) existence of collagen protein thin layer in.

4. method according to claim 3, the wavelength of wherein said blue light is 390 nanometers.

5. method according to claim 2, the wavelength of wherein said green glow is 530 nanometers, and the wavelength of infrared light is 780 nanometers.

6. method according to claim 1, wherein step f) comprise the distributed in three dimensions determining the coefficient of refraction in irradiated corneal moieties from the spatial distribution of the optical path length in irradiated corneal moieties further.

7. method according to claim 1, wherein said ultrared wave-length coverage is 750-800nm.

8. method according to claim 7, wherein said ultrared wavelength is 780nm.

9. method according to claim 1, wherein said infrared ray sends as pulse, and has the energy level being at least 0.2nJ.

10. one kind for making cornea eye (14,56,732) equipment of topography, described cornea (14,56,732) interior zone (13) that there are front surface (12), rear surface (16) and be positioned between described front surface (12) and rear surface (16), this equipment comprises:

A) for irradiating described cornea (14,56,732) laser instrument (704) of selected part, it uses has directly from irradiated cornea (14,56,732) infrared ray (40,720) producing the wavelength of fluorescence and second_harmonic generation imaging signal by nonlinear optics process in part irradiates;

B) for the focusing arrangement (742,744) of focused IR line (40,720) in the selected part of cornea (14,56,732);

C) scanning and control unit (706), by using infrared ray (40,720) the scanning cornea (14,56 focused on, 732) the multiple Different Plane perpendicular to eye optical axis in selected part, described multiple plane and following partial intersection:

1) Part I of described front surface (12) and the Part I of described interior zone (13),

2) Part II of described front surface (12), the Part II of described interior zone (13) and the Part I of described rear surface (16), and

3) Part II of described rear surface (16) and the Part III of described interior zone (13),

D) for detecting the photodetector (786) of fluorescence and the second_harmonic generation imaging signal produced from irradiated cornea (14,56,732) part; And

E) computerized control unit, its:

1) assessment is from the second_harmonic generation imaging signal of irradiated cornea (14,56,732) part generation;

2) according to the measured value determining the shape of front surface (12) and rear surface (16) and the spatial discrimination thickness of irradiated cornea (14,56,732) from the autofluorescence detected;

3) from second_harmonic generation imaging signal, determine the three-layer laminated structure of the corneal stromal tissue in irradiated cornea (14,56,732) part;

4) spatial distribution by using finite element modeling to draw reflectance n (x, y), determines the optical path length (76) of irradiated cornea (14,56,732) part from the fluorescence detected;

5) from the irradiated cornea (14 generated, 56,732) topography of front surface (12), rear surface (16) and interior zone (13) is generated in the spatial distribution of the optical path length (76) of part.